Loading…
Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus
Recent findings from studies of two families have shown that mutations in the GABA A -receptor γ2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS + ), including an individual with severe...
Saved in:
| Published in: | American journal of human genetics 2001-12, Vol.70 (2), p.530-536 |
|---|---|
| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | |
|---|---|
| cites | |
| container_end_page | 536 |
| container_issue | 2 |
| container_start_page | 530 |
| container_title | American journal of human genetics |
| container_volume | 70 |
| creator | Harkin, Louise A. Bowser, David N. Dibbens, Leanne M. Singh, Rita Phillips, Fiona Wallace, Robyn H. Richards, Michaella C. Williams, David A. Mulley, John C. Berkovic, Samuel F. Scheffer, Ingrid E. Petrou, Steven |
| description | Recent findings from studies of two families have shown that mutations in the GABA
A
-receptor γ2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS
+
), including an individual with severe myoclonic epilepsy of infancy, in whom a third GABA
A
-receptor γ2-subunit mutation was found. This mutation lies in the intracellular loop between the third and fourth transmembrane domains of the GABA
A
-receptor γ2 subunit and introduces a premature stop codon at Q351 in the mature protein. GABA sensitivity in
Xenopus laevis
oocytes expressing the mutant γ2
Q351X
subunit is completely abolished, and fluorescent-microscopy studies have shown that receptors containing GFP-labeled γ2
Q351X
protein are retained in the lumen of the endoplasmic reticulum. This finding reinforces the involvement of GABA
A
receptors in epilepsy. |
| format | article |
| fullrecord | <record><control><sourceid>pubmedcentral</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_384926</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>pubmedcentral_primary_oai_pubmedcentral_nih_gov_384926</sourcerecordid><originalsourceid>FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_3849263</originalsourceid><addsrcrecordid>eNqljEtOwzAURS0EouGzh7eBSHbS_AYMAmrKsKKdW076Sh5KbMsfULst9sGa6KATxoyOro7uuWKJKPIqLUteXLOEc56lTdZUC3bn_QfnQtQ8v2ULIaplXfAmYfPORT2oQEaDOUAYEdbtc9umbzigDcbBz3cG29hHTQFIg4JOzTQd4YvCCGvU6NREJ9zDytKE1l9Mh707b9ginaJDD5sp-gd2c1CTx8cL79lTt9q9vKY29jPuB9ThXJPW0azcURpF8q_RNMp38ynzetlkZf7f_y8aAGMG</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus</title><source>BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS</source><source>PubMed Central</source><creator>Harkin, Louise A. ; Bowser, David N. ; Dibbens, Leanne M. ; Singh, Rita ; Phillips, Fiona ; Wallace, Robyn H. ; Richards, Michaella C. ; Williams, David A. ; Mulley, John C. ; Berkovic, Samuel F. ; Scheffer, Ingrid E. ; Petrou, Steven</creator><creatorcontrib>Harkin, Louise A. ; Bowser, David N. ; Dibbens, Leanne M. ; Singh, Rita ; Phillips, Fiona ; Wallace, Robyn H. ; Richards, Michaella C. ; Williams, David A. ; Mulley, John C. ; Berkovic, Samuel F. ; Scheffer, Ingrid E. ; Petrou, Steven</creatorcontrib><description>Recent findings from studies of two families have shown that mutations in the GABA
A
-receptor γ2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS
+
), including an individual with severe myoclonic epilepsy of infancy, in whom a third GABA
A
-receptor γ2-subunit mutation was found. This mutation lies in the intracellular loop between the third and fourth transmembrane domains of the GABA
A
-receptor γ2 subunit and introduces a premature stop codon at Q351 in the mature protein. GABA sensitivity in
Xenopus laevis
oocytes expressing the mutant γ2
Q351X
subunit is completely abolished, and fluorescent-microscopy studies have shown that receptors containing GFP-labeled γ2
Q351X
protein are retained in the lumen of the endoplasmic reticulum. This finding reinforces the involvement of GABA
A
receptors in epilepsy.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>PMID: 11748509</identifier><language>eng</language><publisher>The American Society of Human Genetics</publisher><ispartof>American journal of human genetics, 2001-12, Vol.70 (2), p.530-536</ispartof><rights>2002 by The American Society of Human Genetics. All rights reserved. 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC384926/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC384926/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,53791,53793</link.rule.ids></links><search><creatorcontrib>Harkin, Louise A.</creatorcontrib><creatorcontrib>Bowser, David N.</creatorcontrib><creatorcontrib>Dibbens, Leanne M.</creatorcontrib><creatorcontrib>Singh, Rita</creatorcontrib><creatorcontrib>Phillips, Fiona</creatorcontrib><creatorcontrib>Wallace, Robyn H.</creatorcontrib><creatorcontrib>Richards, Michaella C.</creatorcontrib><creatorcontrib>Williams, David A.</creatorcontrib><creatorcontrib>Mulley, John C.</creatorcontrib><creatorcontrib>Berkovic, Samuel F.</creatorcontrib><creatorcontrib>Scheffer, Ingrid E.</creatorcontrib><creatorcontrib>Petrou, Steven</creatorcontrib><title>Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus</title><title>American journal of human genetics</title><description>Recent findings from studies of two families have shown that mutations in the GABA
A
-receptor γ2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS
+
), including an individual with severe myoclonic epilepsy of infancy, in whom a third GABA
A
-receptor γ2-subunit mutation was found. This mutation lies in the intracellular loop between the third and fourth transmembrane domains of the GABA
A
-receptor γ2 subunit and introduces a premature stop codon at Q351 in the mature protein. GABA sensitivity in
Xenopus laevis
oocytes expressing the mutant γ2
Q351X
subunit is completely abolished, and fluorescent-microscopy studies have shown that receptors containing GFP-labeled γ2
Q351X
protein are retained in the lumen of the endoplasmic reticulum. This finding reinforces the involvement of GABA
A
receptors in epilepsy.</description><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNqljEtOwzAURS0EouGzh7eBSHbS_AYMAmrKsKKdW076Sh5KbMsfULst9sGa6KATxoyOro7uuWKJKPIqLUteXLOEc56lTdZUC3bn_QfnQtQ8v2ULIaplXfAmYfPORT2oQEaDOUAYEdbtc9umbzigDcbBz3cG29hHTQFIg4JOzTQd4YvCCGvU6NREJ9zDytKE1l9Mh707b9ginaJDD5sp-gd2c1CTx8cL79lTt9q9vKY29jPuB9ThXJPW0azcURpF8q_RNMp38ynzetlkZf7f_y8aAGMG</recordid><startdate>20011217</startdate><enddate>20011217</enddate><creator>Harkin, Louise A.</creator><creator>Bowser, David N.</creator><creator>Dibbens, Leanne M.</creator><creator>Singh, Rita</creator><creator>Phillips, Fiona</creator><creator>Wallace, Robyn H.</creator><creator>Richards, Michaella C.</creator><creator>Williams, David A.</creator><creator>Mulley, John C.</creator><creator>Berkovic, Samuel F.</creator><creator>Scheffer, Ingrid E.</creator><creator>Petrou, Steven</creator><general>The American Society of Human Genetics</general><scope>5PM</scope></search><sort><creationdate>20011217</creationdate><title>Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus</title><author>Harkin, Louise A. ; Bowser, David N. ; Dibbens, Leanne M. ; Singh, Rita ; Phillips, Fiona ; Wallace, Robyn H. ; Richards, Michaella C. ; Williams, David A. ; Mulley, John C. ; Berkovic, Samuel F. ; Scheffer, Ingrid E. ; Petrou, Steven</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_3849263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harkin, Louise A.</creatorcontrib><creatorcontrib>Bowser, David N.</creatorcontrib><creatorcontrib>Dibbens, Leanne M.</creatorcontrib><creatorcontrib>Singh, Rita</creatorcontrib><creatorcontrib>Phillips, Fiona</creatorcontrib><creatorcontrib>Wallace, Robyn H.</creatorcontrib><creatorcontrib>Richards, Michaella C.</creatorcontrib><creatorcontrib>Williams, David A.</creatorcontrib><creatorcontrib>Mulley, John C.</creatorcontrib><creatorcontrib>Berkovic, Samuel F.</creatorcontrib><creatorcontrib>Scheffer, Ingrid E.</creatorcontrib><creatorcontrib>Petrou, Steven</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harkin, Louise A.</au><au>Bowser, David N.</au><au>Dibbens, Leanne M.</au><au>Singh, Rita</au><au>Phillips, Fiona</au><au>Wallace, Robyn H.</au><au>Richards, Michaella C.</au><au>Williams, David A.</au><au>Mulley, John C.</au><au>Berkovic, Samuel F.</au><au>Scheffer, Ingrid E.</au><au>Petrou, Steven</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus</atitle><jtitle>American journal of human genetics</jtitle><date>2001-12-17</date><risdate>2001</risdate><volume>70</volume><issue>2</issue><spage>530</spage><epage>536</epage><pages>530-536</pages><issn>0002-9297</issn><eissn>1537-6605</eissn><abstract>Recent findings from studies of two families have shown that mutations in the GABA
A
-receptor γ2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS
+
), including an individual with severe myoclonic epilepsy of infancy, in whom a third GABA
A
-receptor γ2-subunit mutation was found. This mutation lies in the intracellular loop between the third and fourth transmembrane domains of the GABA
A
-receptor γ2 subunit and introduces a premature stop codon at Q351 in the mature protein. GABA sensitivity in
Xenopus laevis
oocytes expressing the mutant γ2
Q351X
subunit is completely abolished, and fluorescent-microscopy studies have shown that receptors containing GFP-labeled γ2
Q351X
protein are retained in the lumen of the endoplasmic reticulum. This finding reinforces the involvement of GABA
A
receptors in epilepsy.</abstract><pub>The American Society of Human Genetics</pub><pmid>11748509</pmid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0002-9297 |
| ispartof | American journal of human genetics, 2001-12, Vol.70 (2), p.530-536 |
| issn | 0002-9297 1537-6605 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_384926 |
| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS; PubMed Central |
| title | Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T15%3A58%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmedcentral&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Truncation%20of%20the%20GABAA-Receptor%20%CE%B32%20Subunit%20in%20a%20Family%20with%20Generalized%20Epilepsy%20with%20Febrile%20Seizures%20Plus&rft.jtitle=American%20journal%20of%20human%20genetics&rft.au=Harkin,%20Louise%20A.&rft.date=2001-12-17&rft.volume=70&rft.issue=2&rft.spage=530&rft.epage=536&rft.pages=530-536&rft.issn=0002-9297&rft.eissn=1537-6605&rft_id=info:doi/&rft_dat=%3Cpubmedcentral%3Epubmedcentral_primary_oai_pubmedcentral_nih_gov_384926%3C/pubmedcentral%3E%3Cgrp_id%3Ecdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_3849263%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/11748509&rfr_iscdi=true |